Thyroid Pharmacology Flashcards
T/F iodide is the rate limiting step in thyroid hormon syntehsis
T
T/F more t4 than than t3 is produced by thyroid
T
T/F T4 and T3 are largely protein bound
T
T/F TSH is low in hypothyroidism
F
T4 half life
7 days –> longer than 1 day T3
Why is there high TSH/TRH in hypothyroidism?
body trying to compensate for low T3/T4
Goal of thyroid hormone replacement
not a cure, just replacement
Why is hypothyroidism treated with T4 vs T3
half life is longer, peripheral conversion of T4 to T3
Why do some people have persistence of symptoms after T4 tx?
small studies show no benefit of combo tx, might also depend on polymorphisms of type 2 deoiodinase gene
Indications for T3
thyroid cancer pts before radioactive iodine therapy and scans, myxedema coma
Side effects of levothyroxin
from inappropriate dosing, can also have coloring dye sensitivity
Starting dose of levothyroxin depends on:
age, degree of thyroid failure –> older or cardiac disease, use smaller doses
IV dose of levothyroxin
75% of oral dose
Target TSH on tx
6 weeks/half lives and TSH target of .5-5 (but best is .5-2.5
In which situation can TSH not be trusted?
secondary hypothyroidism –> need to check thyroid hormone levels
Why would TSH on tx be higher than expected?
noncompliance, drugs/conditions that decrease LT4 absorption, drugs that increase LT4 metabolism, increase TBG, progression of endogenous thyroid disease
Drugs that decrease LT4 absorption:
iron, calcium carbonate, aluminum hydroxide, sucralfate, colestipol, ppi –> can be an issue with maternal supplements
Conditions that decrease LT4 absoprtion:
small intestine disease,
Drugs that increase LT4 metabolism
phenocarbitol, carbamazepine, phenytoin, rifampin
Causes of increase TBG
pregnancy, estrogens, hepatitis
Why would TSH on tx be lower than expected?
dopamine, high dose glucocorticoids, decrease TBG, self administration of excess LT4, reactivation of Graves’ or development of nodules
causes of decrease TBG
androgens, nephrotic syndrome, chronic liver disease, sever systemic illness
Tx of myxedema coma
iv hydrocortisone, LT4 and LT3, tx of precipitating factors like infection
Drug to avoid in myxedma coma
sedatives b/c of decrease drug metabolism
Antithyroid drugs block:
- oxidation and iodination of Tg
- iodotyrosine coupling to form T3/T4
e.g. PTU, tapazole
Indications of antithyroid drugs
Graves: cool down pt before RAI or surgery, adults who may achieve remission, children and adolescents
Antithyroid drug of choice
methimazole –> longer half life than PTU –> both have latent period of improvement
T/F methimazole is protein bound
F –> PTU is which is useful in tx of pregnant women in 1st trimester (can’t cross placenta)
PTU increases/decreases T4 to T3 conversion
decreases
Side effects of PTU
lupus, vasculitis, hepatitis –> more than methimazole
T/F frequency of side effects of methimazole are dose related
T –> vs PTU which is pretty random
Use methimazole in graves’ always except in:
1st trimester pregnancy, thyroid storm, adverse effects to methimazole
Major side effects of antithyroid drugs
agranulocytosis, PTU hepatitis, MMI cholestasis, vasculitis, polyarthritis
Tx of agranulocytosis
stop antitoyroid drug, broad spectrum ab, hospitalize if granulocyte<500
Drugs that inhibit T4 to T3 conversion
PTU, glucocorticoids,propanolol
Tx of thyrotoxicosis
beta blockers b/c not an issue of thyroid proliferation but simply higher release of thyroid hormone from cells –> atenolol or metoprolol
Tx of subacute thyroiditis
NSAID
Tx of thyroid storm
PTU/MMI, propanolol, hydrocortisone, SSKI drops
Iodide uptake mediated by ___ in normal thyroid
Na+/I- symporter NIS
Wolff-Chaikoff Effect
excess iodide transiently inhibits thyroid iodide organification –> in normal thyroid, gland can regulate this inhibitory effect // in individuals with underlying autoimmune disease, this suppressive effect may persist even after iodine levels normalize
T/F wolff chiakoff can be beneficial in tx of graves
T –> persistent suppression can decrease thyroid hormone synthesis, supporting anti-thyroid tx
Jod-Basedow effect
thyrotoxicosis produced by iodine exposure –> in nodules
I131
emits gamma and beta particles for dx and tx –> dose dependent effect
Contraindications of I131
breastfeeding/pregnant women, children
T/F goal in graves is hypothyroidism
T
Amiodoarone
anti-arrhythmia that is 37% iodine –> can cause hypo or hyperthyroidism
Type 1 hyperthyroidism: in pts with underlying thyroid nodular disease, increased thyroid hormone production –> iodine effect
Type 2 hyperthyroidism: in pts with normal thyroid –> destructive thyroiditis with increased thyroid hormone release –> direct toxic effect of amiodorone
rTSH
used in thyroid cancer pts for dx and imaging –> avoids symptomatic hypothyroidism
TSH stimulates uptake of iodine //in pts with residual thyroid cancer, want to stimulate uptake of iodine as much as possible before doing scan –> normally let the pt go hypothyroid and then give iodine to measure effect –> now can give rTSH to avoid hypothyroid effects while still letting endogenous TSH to drop before the test
